Differential gene expression remains the most central and unifying concept of cellular differentiation and embryonic development both normal and abnormal. If we can first understand and then control differential gene activity, malignant proliferations of human cells such as leukemia and solid tumors as well as defective differentiations leading to life-threatening biochemical or morphological birth defects may prove reversible. Differential gene activity is expressed in part through transcription products, messenger RNAs, which specify the sequences in which amino acids polymerize to form proteins. This research proposal intends to examine both the messenger RNA products of the genes for histones and the genes themselves. The messenger for histone IV will be completely sequenced and information gained about both translated and non-translated RNA sequences. Comparative studies will directly measure rates of evolutionary mutation in both regions of the sequence. The reiterated DNA specifying histone templates will be purified by buoyant density centrifugation and used to determine the linkage, if any, between genes for individual histones and the clustered histone and spacer sequences. The purified histone DNA will be used to search for nuclear precursors of cytoplasmic templates in nuclear RNA and in the products of isolated nuclei.